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vary from continuous treatment for 3 to 6 months with monotherapy
to immediate discontinuation after surgery. These agents are not indicated for the treatment of inactive or calcified cysts, except in complicated lesions. Monitoring of leukocyte counts and LFTs are essential
because side effects include neutropenia, hepatotoxicity, nausea, and
alopecia. More recent data suggest that albendazole combined with
the antiparasitic drug praziquantel (a synthetic isoquinoline-pyrazine
derivative, 25 mg/kg/day orally in varying regimens) is more effective
than albendazole alone. When used without other therapeutic modalities, the success rate of monotherapy with these drugs is approximately 30%; thus it is only recommended in specific smaller (<5 cm)
liver cysts (WHO cystic echinococcosis type 1 [CE1]). Therefore
additional percutaneous or surgical therapy should be used in conjunction with medical treatment (see Table 1). When combined with
surgery, albendazole has been shown to both reduce the number of
viable cysts at the time of surgery and decrease disease recurrence.
Percutaneous Therapy
Percutaneous treatment of hepatic cystic echinococcosis has become
increasingly acceptable in recent years for carefully selected patients.
Therapy can consist of either PAIR aimed at destroying the germinal
cyst layer or needle decompression and catheter drainage with the
goal of evacuating the entire endocyst. Catheter drainage is generally
reserved for giant (>10 cm) unilocular cysts. In this procedure, the
catheter is left in place until the daily output is less than 10 mL per
day. Current consensus guidelines recommend PAIR for patients
who are at high-risk or patients who refuse surgery, fail medical
management alone, have infected cysts, or experience recurrence
after surgery. Cysts that are greater than 5 cm and classified as CE1,
CE2, or CE3 are most amenable to primary treatment with PAIR
plus a benzimidazole. PAIR is contraindicated in patients with biliary
fistulae, complicated cysts, and inaccessible or high-risk locations
(superficial) and in those with CE4 or CE5, inactive, or calcified
cysts. Symptomatic pregnant women and children older than 3 years
of age should be evaluated with care, and individual treatment decisions should be made regarding the use of PAIR.
The PAIR procedure consists of percutaneous puncture and
aspiration of the cyst with ultrasound guidance followed by injection or instillation of an indwelling scolicidal solution for 10 to 30
minutes, and then reaspiration of the agent and final irrigation with
0.9% saline solution. Protoscolicides typically used include either
hypertonic 20% saline or absolute alcohol. The goal is to reduce the
size and volume of the cyst, detach the inner germinal layer from
the pericyst with the scolicidal agent, thicken the cyst wall, and
eventually solidify the cyst. To prevent spillage of protoscoleces and
improve efficacy of the therapy, albendazole should be administered
before PAIR and for up to 1 month after the procedure. Whether
preprocedural albendazole should be started a few hours or up to
1 week before PAIR is unclear. However, data have shown that combined treatment of PAIR plus albendazole is superior to either alone.
More than 4000 PAIR interventions have been performed over the
past 20 years, proving the safety of the procedure. A 2003 meta-analysis compared PAIR plus albendazole or mebendazole with surgical
therapy and found that PAIR and chemotherapy had a higher cure
rate, less recurrence, fewer complications, and decreased length of
stay. However, the surgical group was a historic control of mixed
cases performed before 2001, and more than half of the patients
did not receive any antihelminthic drug therapy, the standard of
care, which makes interpretation of the results difficult. Although
PAIR and percutaneous drainage have been proven to be relatively
safe, better data on the various therapies will be required before the
optimal treatment of hepatic hydatid cysts can be fully determined.
Operative Therapy
Surgical management of echinococcal cyst disease of the liver was
the only treatment option before the 1980s and has long been the
primary therapeutic modality. Indications for surgery include large
CE2 to CE3 cysts with multiple daughter cysts; superficial singular
cysts at risk for spontaneous or traumatic rupture; infected cysts or
those with biliary communication, particularly when percutaneous
therapy is not available or possible; and cysts with a mass effect on
adjacent vital organs. Evaluation of cyst type, size, location, presence
or absence of complications, and patient factors (comorbidities, compliance) should be considered when choosing surgical intervention
versus other therapies. Operative management is generally contraindicated in patients who are unfit for surgery or those with inactive
asymptomatic cysts, poorly located cysts, and very small cysts. The
tenets of treatment with surgery remain to completely inactivate
the scolices, eliminate the parasite and viable cyst contents, prevent
recurrence or spillage of cyst contents, manage the cyst cavity, and
prevent untoward morbidity and mortality.
A variety of surgical techniques exists, including open and
laparoscopic cyst evacuation, pericystectomy, liver resection, and
transplantation. Proper preoperative evaluation of the location of bile
ducts and vascular structures with ultrasound, CT, or MRI should
be obtained. If a biliary communication is suspected, preprocedural
ERCP should be performed. The use of intraoperative ultrasound
also is helpful in identifying and avoiding key structures. These
operative therapies all should be used in conjunction with a benzimidazole (administered for at least 1 day before surgery and for up to
1 month after surgery, if viable scolices are present) to decrease the
risks of residual or recurrent disease.
The surgical treatment can be categorized as conservative or rad-
ical based on the extent of the operation. The conservative approach
involves partial or subtotal resection of the cyst, resecting the endocyst, and leaving the pericyst behind. The residual cavity is generally
dealt with by securing an omental pedicle flap into the cavity. The
radical approach is aimed at removing the entire cyst, including the
pericyst, which can be performed as a pericystectomy, a segmental
or lobar liver resection, or liver transplantation in rare scenarios.
Although the radical approach has a decreased risk of recurrence, an
increased risk of morbidity is present with this approach because of
the more aggressive nature of the surgical intervention.
Scolecoidal Agents
Inactivation of protoscolices and prevention of their spillage during
surgery with scolecoidal agents is strongly recommended. In the past,
considerable controversy existed over the use and type of scolecoidal
agents. Formalin, cetrimide, and chlorhexidine all have been used,
but the safety and efficacy of these agents have not been established.
The WHO recommends 20% hypertonic saline solution that should
be in contact with the germinal layer of the cyst for at least 15 minutes before intervention. Hypertonic saline solution and other agents
should be avoided in patients with cystobiliary fistulas because of
the risk of chemically induced sclerosing cholangitis if the agent
enters the biliary tract. Care should be taken to prevent the develop
ment of hypernatremia, another potential side effect of hypertonic
saline solution that is seen with overuse. Peritoneal contents can be
protected with protoscolicide-soaked surgical sponges. In addition,
preevacuation injection of hypertonic saline solution into the cyst
should be avoided because intracyst pressure is already high and may
increase the likelihood of protoscolex spillage. A meticulous surgical technique is warranted rather than overreliance on scolecoidal
agents. If spillage does occur, the peritoneum should be washed with
hypertonic saline, and patients should be treated with albendazole
(3–6 months) and a brief course of praziquantel (7 days).
Open Cyst Evacuation
As one of the safest surgical approaches, open evacuation of hydatid
cysts is considered a conservative surgical therapy and is most suitable for peripherally located cysts on or near the surface of the liver.
When anterior, an abdominal approach is best, whereas cysts in
segments VI and VII are more amenable to a lateral flank approach.
Figure 4A depicts evacuation of the cyst contents via aspiration;
subsequent injection of a scolecoidal agent is optional at the time.
Note that the field is lined with hypertonic saline solution–soaked
-
360 MANAGEMENT OF ECHINOCOCCAL CYST DISEASE OF THE LIVER
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AB
FIG. 4 (A) Open cyst evacuation shows cyst aspiration (top left), suction removal of daughter cysts (top right), resection of the active cyst lining (bottom
left), and omental packing with suture tacking (bottom right). (B) Operative picture shows the daughter cysts. (From Cameron JL, Sandone C. Atlas of Surger y:
Gallbladder and Biliary Tract, the Liver Portosystemic Shunts, the Pancreas. Philadelphia: BC Decker; 1990.)
gauze in the event of spillage. The cyst cavity is then opened, and the
contents are aspirated with a large suction device with high negative
pressure (Fig. 4B). Removal of daughter cysts, resection of the active
cyst lining, and meticulous clearance of any remaining debris can be
performed once the cyst is completely opened. The cyst may then
be irrigated with a scolecoidal agent, as described previously, and
packed with omentum.
However, if the cyst fluid is bile stained or communication
with the bile ducts was shown on preoperative ERCP, intracavity
scolecoidal agents should be avoided. Simple closure of any biliary
connection should be performed with absorbable sutures, and the
cyst cavity should be filled with omentum. If the cystobiliary fistula
cannot be easily closed, external drainage with a closed-suction drain
may be warranted. A cystobiliary fistula also should be suspected
in large cysts (>7.5 cm) for which the incidence is as high as 80%,
prompting a search for biliary communication. The application of
diluted hydrogen peroxide into the cyst cavity can help identify any
small biliary communication.
Minimally Invasive Cyst Evacuation
A minimally invasive approach to echinococcal liver disease uses
the same principles as open surgery. Several reports have shown that
carefully selected patients with peripherally located hepatic hydatid
cysts may be safely managed with laparoscopic cyst evacuation. Anterior cysts without thick calcified walls and those in segments VI and
VII (with a right lateral approach) are particularly amenable to this
approach. One laparoscopic technique uses an 11-mm trocar placed
just above the cyst, through which 10% povidone-iodine–soaked
sponges are placed to act as a scolecoidal agent. The cyst is then
punctured with a 14-gauge needle and aspirated, causing the endocyst to shrink away from the wall and rest at the bottom of the cyst.
The 11-mm trocar is then upsized to 18-mm so the germinal membrane can be aspirated. The laparoscope is then inserted directly into
the cyst to identify any remaining daughter cysts or biliary fistulae,
and the cyst cavity is irrigated with 20% hypertonic saline solution.
Excision of the cyst wall followed by omentoplasty or closed-suction
drainage is then performed to complete the procedure.
Advantages to the laparoscopic approach include reduced hospital stay, decreased hospital cost, and earlier return to productive
activity. With laparoscopy, short operative times (less than 90
minutes) and low complication rates also have been reported. In
properly selected patients with uncomplicated cysts, conversion to
an open procedure should occur in less than 5% of cases. Although
no large case series, retrospective studies, or prospective studies exist
regarding a robotic approach to hydatid cysts, one study from Italy
consisting of 15 patients undergoing major hepatectomy, partial
hepatectomy, and cyst-pericystectomies demonstrated that a robotic
approach to hydatid cysts is safe and effective with shorter postoperative stay, quick return to daily activity, and absence of surgical site
recurrence.
Despite improved visualization, these minimally invasive
approaches have not gained widespread acceptance because of the
relative inability to avoid or control peritoneal spillage in the setting of
high intraabdominal pressures from the pneumoperitoneum (a limited
area for manipulation) and difficulty aspirating thick cyst contents.
Techniques to minimize spillage of cyst contents include insertion of
iodine-soaked sponges as described, fixing the cyst to the abdominal
wall, lavage with scolicidal agents, and creation of a scolicidal pool
around the liver by operating in the reverse Trendelenburg position.
Whatever approach is used, oral albendazole both before and after surgery is still indicated. In addition to simple drainage, laparoscopic partial cystectomy and even total pericystectomy also have been described.
Pericystectomy
Pericystectomy involves complete resection of the cyst wall either
closed, without entering the cyst cavity itself, or open, by sterilizing
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AB
FIG. 5 (A) Pericystectomy depicting removal of the calcified pericyst (top), suture closure of a communicating bile duct (middle), and (optional) closure
of the cavity over a drain (bottom). (B) Operative picture shows cyst removal. (From Cameron JL, Sandone C. Atlas of Surgery: Gallbladder and Biliary Tract, the
Liver Portasystemic Shunts, the Pancreas. Philadelphia: BC Decker; 1990.)
the contents with protoscolicidal agents, evacuating the cyst tissue,
and then removing the pericyst tissue (Fig. 5A). This procedure can
be performed with electrocautery or a dissector, either along a plane
outside the pericyst or along the cyst wall itself. When dissecting
around the cyst, some authors advocate use of a cleavage plane
between the inner layer of the host’s reaction toward the parasite and
the outer layer, or adventitia, which limits damage to the liver parenchyma and allows safer removal (Fig. 5B). Similar to cyst evacuation,
pericystectomy is best performed on cysts along the periphery of
the liver.
The advantage of this procedure over simple cyst drainage is a
decreased risk of cyst content spillage into the peritoneal cavity when
performed as a closed pericystectomy, which avoids potential anaphylaxis and decreases the risk of recurrence. Complete removal of
the adventitia and elimination of the need for scolecoidal agents can
be achieved with a closed procedure. The disadvantages of pericystectomy are an increased risk of bleeding or damage to bile ducts in
proximity to the cyst wall because of the need for hepatic parenchymal transection. When encountered, vascular and biliary structures
can be controlled with clips or sutures as illustrated in Figure 5A, and
the cavity can be closed over a drain.
In a study comparing closed cyst resection with pericystectomy
versus open cyst resection, closed cyst resection was demonstrated
to have 0% recurrence rate at 5 and 10 years versus 18% and 27%
recurrence in the open cyst resection group, respectively. However,
the closed cyst resection group had a high rate of major morbidity
at 19% compared with the open resection group at 5%. Despite the
higher risk of morbidity, pericystectomy is preferred to cyst evacuation because of a lower risk of secondary echinococcosis from
protoscolex dissemination. However, the conservative approach of
cyst evacuation is well suited for endemic areas, where operations are
performed by nonspecialty-trained general surgeons and resources
are limited.
Liver Resection/Transplantation
Another “radical” surgical approach to the management of hepatic
echinococcal cyst disease is liver resection, which can range from
nonanatomic wedge resection to formal hemihepatectomy. Although
formal liver resection for benign disease may seem excessive, hepatic
resection is now very safe, especially when performed by surgeons
and centers with expertise in liver surgery. Multiple indications for
liver resection exist, including complicated cysts with large biliary
fistulae and small peripheral cysts where the cut surface of the liver
is less with resection than with pericystectomy. Liver resection also
should be considered for multiple cysts within proximity to one
another or major structures, such as portal or hepatic veins or bile
ducts, or when the resection would be relatively safe as seen with
cysts confined to the left lateral segments II or III. Patients with
recurrent disease who have failed more conservative management
also are candidates for liver resection. Formal resection of the liver
should be initiated only if complete excision of all cysts is possible.
In one study, operative time, length of stay, postoperative morbidity,
and cyst recurrence were shown to be increased in patients treated
with liver resection compared with pericystectomy. However, resection avoids pedunculated ischemic hepatic tissue, which can be seen
with pericystectomy.
Perhaps the most radical of surgical management options, liver
transplantation, is rarely indicated in the treatment of hepatic
hydatid disease not amenable to alternative therapies. As opposed to
E. granulosus, which tends to form solitary cysts, E. multilocularis can
produce a more complicated form of the disease with multiple cysts
known as alveolar echinococcosis. These cysts can result in fulminant
liver failure from sclerosing cholangitis, Budd-Chiari syndrome, or
biliary sclerosis. In such unusual cases, orthotropic liver transplantation may be indicated.
SUMMARY
Uncomplicated Disease
Patients with uncomplicated echinococcal cyst disease of the
liver typically are asymptomatic with incidental cyst discovery on
imaging or at abdominal surgery for other reasons. However, they
may present with right upper quadrant pain without fever, chills,
362 MANAGEMENT OF ECHINOCOCCAL CYST DISEASE OF THE LIVER
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jaundice, or cough. A complete history and physical examination
should be performed, laboratory tests including LFTs and serology
should be sent, and the WHO-IWGE type should be determined
with ultrasound imaging or other available studies. For patients
with CE1, CE2, or CE3 (Gharbi types I, III, or II, respectively)
cysts, particularly if they are anterior, peripheral, unilocular, less
than 5 cm, and not heavily calcified, PAIR or minimally invasive
cyst evacuation should be considered depending on local expertise
(Table 3). Alternatively, uncomplicated cases with CE4 or CE5
(Gharbi types IV or V) cysts that are posterior, central, greater
than three in number, large (>5 cm), or calcified should undergo
open evacuation or resection when surgery is indicated. The WHO
guidelines further suggest that in uncomplicated CE4 or CE5 cysts
proven to be inactive, a watch and wait approach may be undertaken with long-term ultrasound imaging follow-up, especially if
local surgical expertise is not available. The decision to perform
cyst evacuation, pericystectomy, or liver resection should be individualized based on patient and cyst characteristics and surgeon
experience.
Complicated Disease
Patients with complicated hepatic hydatid cysts can be secondarily
infected or have biliary obstruction, cystobiliary fistula, or rupture
into the biliary tree, peritoneal cavity, or pleural cavity. Secondary
bacterial infection generally results from biliary communication and
should be treated with appropriate systemic antibiotics and adequate
cyst drainage. In carefully selected patients, percutaneous drainage
may be needed before definitive surgical treatment. In the 5% to 15%
of patients with hydatid cysts on imaging who present with jaundice
or cholangitis, ERCP is indicated to both evaluate potential fistulae
between the cyst and biliary tree and to drain the biliary system with
a stent. A sphincterotomy alone may not provide adequate treatment.
Once drainage is sufficient and cholangitis has resolved, open
cyst evacuation should be performed and the biliary fistulae closed
as described previously. Cyst diameter greater than 7.5 cm is a risk
factor for a biliary-cyst communication, even in asymptomatic
patients, with an 80% likelihood of a fistula being present at surgery.
TABLE 3 Treatment Option Summary
PAIR or Minimally Invasive
Evacuation
UNCOMPLICATED CASES
CE1, CE2, CE3 cysts (Gharbi
I, III, II)
Anterior location Posterior or central location
Small size (<5 cm) Large size (>5 cm)
Few number (1–3 cysts) Multiple (>3 cysts)
Minimal or no calcification Heavy calcification
COMPLICATED CASES
Infected cysts meeting previous
criteria
Albendazole or mebendazole should be used in conjunction with all
treatments.
CE, Cystic echinococosis; PAIR, puncture, aspiration, injection, and
reaspiration.
Open Evacuation or Liver
Resection
CE4 or CE5 cysts (Gharbi IV
or V)
Infected cysts meeting previous
criteria
Biliary or pulmonary
communication
Peritoneal rupture
FIG. 6 CT scan shows rupture of a hepatic cyst through the diaphragm
into the pleural space.
Therefore, one should be prepared to deal with a biliary fistula in the
operating room in patients with large cysts. A concomitant cholecystectomy and intraoperative cholangiogram to ensure complete cyst
debris clearance from the bile ducts also may be required. In rare
instances, a biliary-intestinal anastomosis or liver resection may be
needed to fully treat cystobiliary fistulas.
Complicated disease also occurs occasionally when hydatid
hepatic cysts rupture into the peritoneum or through the diaphragm
into the pleura and lung (Fig. 6), which can result in widespread
disseminated disease. Free rupture of a cyst into the peritoneal cavity
presents with peritonitis, shock, and/or anaphylaxis. Treatment of
the allergic reaction and surgical evacuation are necessary. In these
situations, an open surgical approach is recommended to thoroughly
control the spread of disease throughout the abdomen. Supportive
and intensive therapy also is usually required for the care of these
patients. On the other side of the diaphragm, the workup for patients
with pulmonary complications includes imaging, serology, and bronchoscopy when bronchocystic fistulae are suspected. Benzimidazoles
alone can be used for small, uncomplicated lung cysts. However,
surgical management for these patients often includes evacuation
of cysts from both the liver and the pleural spaces. Open cyst evacuation with closure of the diaphragm and drainage are indicated
but should be as conservative as possible. For extended pulmonary
involvement, severe suppuration, or other complications, pulmonary
resection also may be required. In the chest, as in the abdomen, care
must be taken to prevent spillage of cyst contents to avoid recurrent
infection or anaphylaxis.
RESULTS
Morbidity and Mortality
Advances in the management of patients with echinococcal cyst disease of the liver have decreased the morbidity and mortality of the
disease in recent years. In a 2003 meta-analysis of patients with all
types of disease (uncomplicated and complicated) that compared 769
patients who underwent PAIR with 952 who had surgical intervention, minor and major morbidity rates for each modality were 8% and
13%, respectively, for PAIR as opposed to 25% and 33%, respectively,
for surgery. The overall mortality rate reported in the same study was
0.1% for PAIR and 0.7% for surgery, demonstrating the relative safety
of both approaches. Another study of nearly 3000 patients undergoing percutaneous drainage reported complication rates to be 0.05%
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for anaphylaxis leading to death, 0.38% for major complications
(such as death, secondary echinococcal disease from contamination,
sclerosis), and 1.27% for recurrence. Thus, in patients with uncomplicated hydatid cysts who undergo elective percutaneous or laparoscopic drainage procedures, open evacuation, pericystectomy, wedge
resection, or left lateral sectionectomy, mortality should be very low,
with morbidity rates ranging from 15% to 20%.
A recent retrospective analysis of patients undergoing surgical
treatment of hepatic echinococcal infection reported 0% mortality
and 47% morbidity for resection procedures, but only a 17% morbidity rate for cyst evacuation. Not surprisingly, less invasive techniques
were associated with reduced hospital stay and cost. In patients with
complicated disease who undergo open evacuation, pericystectomy,
or resection, morbidity is in the range of 40% to 50%, and mortality
should be less than 5% (reports range from 0.5% to 4%). The presence of sepsis, peritoneal rupture, underlying comorbid disease, and
malnutrition all are factors that increase mortality.
Long-Term Outcomes
Overall, the long-term cure rate for appropriately and adequately
treated patients with echinococcal hepatic cysts is excellent and
ranges from 90% to 95%. Medical treatment with benzimidazoles
alone should only be used in patients who are otherwise not candidates for percutaneous or surgical therapy because recurrence
rates are approximately 70% to 80%. Therefore, when possible,
medical therapy should be used in combination with a drainage or
resection procedure. In uncomplicated cases, open surgical, minimally invasive surgical, and percutaneous drainage techniques all
have low recurrence rates around 10%. Because of the endemic
nature of this disease and potential for reinfestation, long-term
follow-up is necessary with serologic tests and imaging studies.
WHO guidelines recommend follow-up visits including ultrasound imaging and laboratory tests (CBC and LFTs) every 3 to
6 months initially, and then yearly once the situation is stable. Serologic tests also can be followed. Although a persistence of raised or a
further increase in antibody levels may indicate residual or recurrent
disease, these findings may occur even with full, adequate treatment.
Currently, new antigens show promise for posttreatment monitoring.
Patients with echinococcal cysts complicated by infection, cholangitis, pleural extension, or peritoneal rupture have unique problems. If
the complication such as cholangitis can be treated before definitive
cyst treatment, the long-term outcomes are comparable to those of
uncomplicated echinococcosis. However, patients with rupture into
the pleural cavity or the peritoneum may have a recurrence rate as
high as 25%.
S u g g e S t e d R e a d i n g S
Brunetti E, Kern P, Vuitton DA. Expert consensus for the diagnosis and
treatment of cystic and alveolar echinococcosis in humans. Acta Tropica.
2010;114:1–16.
Julie C, Le Treut YP, Bourgoin S, etal. Closed cyst resection for liver hydatid
disease: a new standard. J Gastrointest Surg. 2021;25:436–446.
Magistri P, Pecchi A, Franceschini E, etal. Not just minor resections: robotic
approach for cystic echinococcosis of the liver. Infection. 2019;47(6):973–
979.
Motie MR, Ghaemi M, Aliakbarian M, etal. Study of radical vs. conservative
surgical treatment of the hepatic hydatid cyst: a 10-year experience. Ind J
Surg. 2010;72(6):448–452.
Nasseri-Moghaddam S, Abrishami A, Taefi A, et al. Percutaneous needle
aspiration, injection, and re-aspiration with or without benzimidazole
coverage for uncomplicated hepatic hydatid cysts. Cochrane Database Syst
Rev. 2011;2011(1):CD003623.
Smego RA Jr, Bhatti S, Khaliq AA, Beg MA. Percutaneous aspiration-
injection-reaspiration drainage plus albendazole or mebendazole
for hepatic cystic echinococcosis: a meta-analysis. Clin Infect Dis.
2003;37(8):1073–1083.
Smego RA, Sebanego P. Treatment options for hepatic cystic echinococcosis.
Int J Inf Dis. 2005;9:60–76.
WHO Informal Working Group: International classification of ultrasound
images in cystic Echinococcus for application in clinical and field epidemiologic settings. Acta Tropica. 2003;85:253–261.
Management of Liver
Hemangioma
Victor M. Zaydfudim, MD, MPH, and Reid B. Adams, MD
OVERVIEW
Liver hemangiomata are the most common benign liver tumors,
with a 2% to 20% overall prevalence in the general population.
Similar to other benign and frequently asymptomatic findings, the
incidental diagnosis of hemangiomas has increased considerably
with more frequent use of cross-sectional imaging. Hemangiomata
are more common in women (5:1 predominance), multifocal in up
to a third of patients, and can be present in combination with other
benign liver tumors. The vast majority of hepatic hemangiomata
are asymptomatic, will remain asymptomatic regardless of size,
and do not require operative management or surveillance. In most
cases, the diagnosis is unequivocally achieved by imaging findings
and expert image interpretation. If operative treatment is pursued, either enucleation or parenchymal resection are reasonable
options based on the location and the extent of the hemangioma.
Pathogenesis and Clinical Presentation
Pathogenesis of liver hemangioma is not clearly understood. Similar
to hemangiomata of other sites, these vascular malformations are
congenital and enlarge by vascular ectasia rather than angiogenesis.
Hemangiomata are structurally surrounded by a pseudocapsule,
with growth of this benign liver tumor results in volumetric expansion and compression of the surrounding tissue by the expanding
hemangioma and its pseudocapsule (Fig. 1). This expanding, but not
invasive, growth compresses the neighboring vascular and biliary
structures, displacing them. As a result, surrounding vascular and
biliary structures are typically not directly involved by the hemangioma. Hemangiomata are multifocal in 10% to 30% of patients and are
present in approximately 10% to 20% of patients with other benign
liver tumors (hepatic adenoma and/or focal nodular hyperplasia).
The pathophysiology of hemangioma growth is not completely
understood. In some, growth is associated with a higher estrogen
state, such as puberty, estrogen replacement therapy, or pregnancy;
however, causality between a higher estrogen state and hemangioma
growth has not been established. Asymptomatic growth of hemangiomata, sometimes to very large sizes, can occur in the elderly.
Interestingly, a decrease in the size of a known hemangioma, at times
with complete involution, has been observed in many patients with
chronic liver disease including both fibrosis and cirrhosis.
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The vast majority of hemangiomata are asymptomatic. These
blood-filled benign liver tumors have the consistency of a soft,
spongelike sac that compresses with pressure. When present, the
most commonly reported symptoms are abdominal pain, discomfort,
fullness, early satiety, and nausea/vomiting. A common postulate to
explain symptoms in patients with hepatic hemangiomata is linked
to the distention and stretch of Glisson’s capsule. The theory is plausible because Glisson’s capsule is innervated; however the majority of
patients with capsular involvement by hemangiomata are not symptomatic. Furthermore, symptoms are frequently absent in patients
with hepatic malignancies that invade and distort Glisson’s capsule.
The term giant is frequently used; however, this term is misleading
and lacks clinical significance. The cutoff for giant classification has
increased from 5 cm (20 to 30 years ago) to over 10 cm currently.
Despite their large size, most hemangiomata are asymptomatic.
Rarely, very large hepatic hemangiomata can cause clinical biliary
obstruction, hepatic venous compression (which can lead to BuddChiari syndrome), or hemangioma thrombocytopenia syndrome
(Kasabach-Merritt syndrome).
As hemangiomas are most frequently asymptomatic, the majority
are identified incidentally during diagnostic imaging for either a
separate problem (e.g., trauma evaluation, nephrolithiasis) or during
FIG. 1 Hemangioma with surrounding pseudocapsule (arrows).
clinical evaluation of epigastric or right upper quadrant pain. The
key feature for management of a hemangioma is establishment of
the correct diagnosis. In most cases, the diagnosis is established by
ultrasonography or cross-sectional diagnostic imaging; rarely the
diagnosis can be challenging and requires more invasive measures.
In even more rare scenarios (commonly sclerosed hepatic hemangioma), preoperative diagnosis is not established, and resection is
pursued for a postoperative diagnosis of hepatic hemangioma. The
diagnosis of atypical hemangioma should raise suspicion and likely
stimulate additional imaging review or investigation.
Overall, four principles should be considered in the management of patients with hemangioma: (1) the majority of patients with
hemangiomata, regardless of size, are asymptomatic and do not
require intervention; (2) a broad differential diagnosis (including gastroesophageal reflux, peptic ulcer disease, gallstone disease) should
be considered in patients who present with epigastric/right upper
quadrant complaints and imaging demonstrating hepatic hemangioma; (3) when resection is considered, both minimally invasive
and open techniques can be pursued, however minimally invasive
approaches should not expand indications for treatment; and (4)
operative treatment of hepatic hemangioma does not improve underlying symptoms in approximately 30% to 50% of selected patients.
Diagnosis
Ultrasonography is diagnostic in many patients with hepatic hemangiomata and is particularly accurate in patients with small hemangiomata (<3 cm). Most smaller hemangiomata are composed of vascular
ectatic architecture without cavernous features, and ultrasound imaging demonstrates a homogenous, hyperechoic, well-circumscribed
liver lesion without posterior acoustic shadowing (Fig. 2A). These
small hepatic hemangiomata can be challenging to classify with single-phase computed tomography (CT), therefore, in the appropriate
clinical setting (e.g., a healthy patient without known chronic liver
disease or malignancy), diagnostic ultrasound rather than further
escalation of cross-sectional imaging can easily establish the correct
diagnosis at minimal cost. Contrast-enhanced ultrasound (CEUS)
can highlight vascular enhancement typical for hemangiomata
(Fig. 2B) and can avoid escalation to cross-sectional imaging. It can
also be used in instances in which contrast cross-sectional imaging is
either nondiagnostic or cannot be technically performed.
Traditional multiphase (triple-phase) CT imaging is diagnostic
for the vast majority of patients with hepatic hemangiomata. The CT
A B
FIG. 2 (A) Ultrasound shows numerous small, hyperechoic, well-circumscribed liver lesions without posterior acoustic shadowing, consistent with multifo-
cal hemangiomata (arrows highlight three lesions). (B) Contrast-enhanced ultrasonography (CEUS) shows differential timing of contrast uptake with intense
uptake by some hemangiomata (yellow arrows) and slower more nodular uptake by another (red arrow) during early arterial-phase contrast injection. Contrast
uptake is homogeneous during portal venous phase and there is contrast retention during the delayed phase (B courtesy Dr. Rachita Khot).
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AB
FIG. 3 Typical peripheral nodular contrast enhancement patterns for hemangioma as visualized with CT arterial phase (A) and MR post-gadolinium (B).
criteria for diagnosis of hemangiomata are: (1) a well-defined and
relatively hypointense liver lesion during the precontrast phase, (2)
early discontinuous nodular peripheral enhancement of the lesion
during the arterial phase (Fig. 3A), and (3) progressive centripetal
contrast enhancement with opacification of the lesion during the
venous phase. CT imaging characteristics can vary between patients,
with differing hemangiomata sizes and internal characteristics of
lesions. Atypical enhancement patterns can be present in both small
and large hepatic hemangiomata. Small hemangiomata frequently
enhance too rapidly to demonstrate nodular filling, while larger
hemangiomata demonstrate variable opacification dependent on the
size of the lesion and internal architecture.
When ultrasound and/or CT demonstrate atypical features, MRI
with vascular (rather than hepatobiliary) contrast can help secure the
diagnosis. The overall accuracy of MRI in establishing the diagnosis
of hemangiomata is very high, with a sensitivity of approximately
90% and a specificity approaching 100%. MRI diagnostic criteria
include lesions that (1) are hypointense relative to normal liver
parenchyma on T1-weighted images, (2) are hyperintense relative
to normal liver on T2-weighted images, (3) are hyperintense relative
to background liver parenchyma on diffusion-weighted imaging
secondary to T2 shine-through, and (4) demonstrate discontinuous
peripheral nodular enhancement with delayed centripetal filling on
T1-weighted sequences after gadolinium administration (Fig. 3B). In
rare circumstances, the diagnosis cannot be established using noninvasive diagnostic imaging. In these exceptional cases, percutaneous
biopsy or resection can be pursued. There is ample evidence that
biopsy of hemangiomata can be performed safely.
in the absence of other potential etiologies, (2) intraparenchymal or
intraperitoneal hemorrhage (exceedingly rare; can be associated with
hemangioma thrombocytopenia syndrome), (3) biliary or hepatic
venous obstruction, or (4) diagnostic uncertainty and inability to
exclude malignancy. The first three of these indications are typically
associated with massive hemangiomas.
Operative management of hepatic hemangiomas can be performed using one of two technical approaches: enucleation or parenchymal resection. As is typical for any liver resection, the principles of
liver surgery including liver mobilization to facilitate exposure, inflow
control, and low central venous pressure anesthesia are paramount.
Cell salvage can be used to allow for autotransfusion of shed blood.
Treatment
The most difficult decision, besides confirming the diagnosis, is
deciding whether treatment is warranted. In most patients (>90%),
irrespective of size, no therapy is indicated or necessary. Treatment
is not indicated in women of childbearing age; there is no need for
cessation or adjustment in oral contraceptives, modification of pregnancy planning, or modification of activity level. Similarly, surveillance in asymptomatic patients with a hemangioma is not warranted.
From a technical perspective, the ability to resect the hemangioma
via a minimally invasive technique (laparoscopic or robotic) should
not expand the indications for resection.
Rarely, after judicious diagnostic evaluation and patient selection,
operative treatment is required. Treatment can be considered for a
narrow range of specific indications: (1) severe persistent symptoms
FIG. 4 Enucleation of hepatic hemangioma can be performed following the
pseudocapsular dissection plane. Inflow occlusion can help facilitate visualization
and dissection of the tumor from the abutting vascular and biliary structures.
(Printed with permission from Anita Impagliazzo.)
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Typically, hemangiomata are surrounded by a pseudocapsule, with
resultant compression rather than invasion of adjoining vascular and
biliary structures. This feature makes enucleation of hemangiomata
technically feasible. Enucleation is particularly attractive as it allows
for use of the natural peritumoral dissection plane for the resection, while preserving functional hepatic parenchyma. Many series
describe enucleation as the dominant resection strategy. Glisson’s
capsule is incised next to the tumor to access the plane between the
hemangioma pseudocapsule and normal parenchyma. The plane is
subsequently further developed with either electrocautery or a clamp
(Fig. 4). More sophisticated parenchymal transection devices are
not typically required during open enucleation of hemangiomata as
retraction of the hemangioma and gentle pressure along the pseudocapsule facilitates separation of the tumor from compressed parenchyma. Vascular structures crossing the resection plane are ligated
and divided. Once the dominant artery that supplies the hemangioma
is divided, the tumor further decompresses, and dissection typically
becomes less challenging; sometimes it is possible to ligate this feeding
vessel early during the course of dissection. Large vascular and biliary
structures (e.g., anterior or posterior branches of the portal vein or
bile duct, the middle hepatic vein) are typically displaced, rather than
involved, and can be preserved. If required for visualization, judicious
inflow control helps visualize the transection plane as well as the
crossing and displaced vascular and biliary structures. Enucleation is
technically feasible for many sublobar tumors; lobar hemangiomata
are more frequently managed with anatomic resection.
Particularly large hemangiomata, those involving the majority
of the liver lobe (or larger), are better suited for anatomic resection.
Ipsilateral ligation of the hepatic artery facilitates decompression of
the hemangioma. In extenuating cases with massive hemangiomata
in which access and control of the hepatic hilum is perceived to be
potentially treacherous, preoperative lobar arterial embolization of
the affected side (typically performed on the day before resection
or the morning of resection) can facilitate hepatic mobilization and
hilar dissection and control. Ligation of the hepatic artery supplying the tumor allows one to compress the hemangioma, similar to
CD
FIG. 5 Ruptured hemangioma in a patient with cirrhosis. Initial CT imaging with hemoperitoneum, enhancement adjacent to liver lesion with internal com-
plexity during arterial phase (A) and progressive centripetal contrast progression during portal venous phase (B). Angiography re-demonstrated a hypervascular tumor (C), and bland transarterial embolization with 150- to 250-micron polyvinyl alcohol particles arrested hemorrhage (D). Given the atypical
presentation in a patient with cirrhosis, a biopsy was performed to confirm the diagnosis of hemangioma.
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squeezing a sponge, decompressing it and making liver mobilization and resection easier. This is an especially helpful maneuver
for massive hemangiomata that fill a substantial space within the
peritoneal cavity. Smaller hemangiomata also can be resected using
either anatomic hepatectomy or non-anatomic hepatectomy. Partial
hepatectomy, rather than enucleation, is more likely to be used in
deeper subcapsular hemangiomas, when indication for resection is
frequently diagnostic equipoise.
Minimally invasive operative approaches can be used depending on surgeon and institutional expertise. Both laparoscopic and
robotic platforms have been used to perform enucleations and
anatomic resections. The use of a minimally invasive approach,
however, should not expand indications for resection. Placement of trocars and positioning depends on the location of the
hemangioma and whether a laparoscopic or robotic approach is
used. Similar to the open operation, inflow control, low central
venous pressure, identification of tumor pseudocapsule, and
dissection along the pseudocapsule plane with ligation of intervening branches are used in minimally invasive enucleation of
hemangiomata.
RUPTURED HEMANGIOMATA,
KASABACH-MERRITT SYNDROME,
AND BUDD-CHIARI SYNDROME
The vast majority of hemangiomata do not rupture, regardless
of tumor size or activity level of the patient. Very rare cases of
tumor rupture present with typical symptoms including abdominal
pain, hemoperitoneum, and hemodynamic instability. Judicious
blood product–directed resuscitation and transarterial embolization
(Fig. 5) can be rapidly performed to arrest hemorrhage. Exploration
with packing is rarely required with the exception of urgent management in a remote location without ability to rapidly transfer the
patient. Rupture of hepatic adenoma or hepatocellular carcinoma
(rather than a hemangioma) should be excluded as these are considerably more frequent causes of hemoperitoneum resulting from a
ruptured liver tumor.
Kasabach-Merritt hemangioma thrombocytopenia syndrome is
similarly very rare. A high index of suspicion in patients with large
hemangiomas and thrombocytopenia can prevent emergent management of disseminated intravascular coagulation in patients with
A
FIG. 6 Establishing the correct diagnosis is critical in the management of liver hemangiomata. Sclerosed or hyalinized hemangiomata are particularly
challenging to diagnose prospectively with imaging; either biopsy or resection are pursued in situations with diagnostic equipoise. (A) An atypical pattern
of enhancement without the typical vascular pattern during either CT or MRI resulted in resection in this patient with a sclerosed hemangioma. (B) In
patients with a personal history of malignancy, new or growing liver lesions should raise suspicion for metastasis, as in this patient with a metastatic gastrointestinal stromal tumor (lesion with peripheral nodular enhancement). (C) Thorough diagnostic evaluation, including consideration for percutaneous or
endovascular biopsy, should be undertaken in patients with atypical imaging findings, as in this patient referred for sarcoma with an evaluation diagnostic for
a hemangioma.
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end-stage hematologic disarray. Resection, if technically permissible,
is the preferred treatment strategy in patients with hemangioma
thrombocytopenia syndrome. Thromboelastography or rotational
thromboelastometry can help manage perioperative coagulopathy;
the coagulopathy resolves after removal of the hemangioma. In a very
rare patient with a truly unresectable hemangioma in conjunction
with hemangioma thrombocytopenia syndrome, transhepatic embolization with adjunct glucocorticoids, propranolol, and cytotoxic
therapy has been reported to achieve resolution of the coagulopathy.
Obstruction of hepatic venous outflow with resultant BuddChiari pathophysiology is an extremely rare manifestation of hepatic
hemangioma. In case reports, this exceedingly rare manifestation of a
hemangioma has been addressed with liver resection (if lobar hepatic
outflow can be preserved) or, in even fewer cases, transplantation.
Case reports of endovascular stenting have been described without
medium- or long-term outcome data.
MASQUERADING LESIONS
Establishing the correct diagnosis is arguably the most critical
aspect in management of liver hemangiomata. Appropriate clinical
suspicion is imperative in cases of diagnostic equipoise. The term
atypical hemangioma is nonspecific and should be avoided. As
hemangiomata typically decrease in size and involute in patients with
cirrhosis, small hypervascular lesions in this patient population are
most commonly either regenerative nodules or hepatocellular carcinoma. Conversely, small hemangiomata can mimic hepatocellular
carcinoma in patients with non-cirrhotic liver disease. In patients
at risk for hepatic adenoma, particularly patients with nonalcoholic
fatty liver disease, atypical hemangioma must be differentiated from
adenoma. Sclerosed, thrombosed, or hyalinized hemangiomata can
mimic a variety of primary and metastatic hepatic malignancies and
can be a particular diagnostic challenge (Fig. 6A). Review of prior
imaging with establishment of the diagnosis using retrospective
comparison to historic imaging is the most reliable noninvasive diagnostic method. Any imaging features of capsular retraction or internal complexity (with atypical characteristics) should be concerning
for possible malignancy. A personal history of malignancy with new
or growing atypical liver lesions should be concerning for metastatic
disease rather than a hemangioma (Fig. 6B).
Questions of diagnostic equipoise can be resolved with appropriate
consideration of the patient’s presentation history, review of prior
imaging, and pursuit of repeat dedicated imaging. If diagnostic imaging remains inconclusive and concern for a worrisome lesion persists
(Fig. 6C), either biopsy or resection should be pursued.
S u g g e S t e d R e a d i n g S
Abdel Wahab M, El Nakeeb A, Ali MA, etal. Surgical management of giant
hepatic hemangioma: single center’s experience with 144 patients. J
Gastrointest Surg. 2018;22:849–858.
Hu M, Chen K, Zhang X, Li C, Song D, Liu R. Robotic, laparoscopic, or open
hemihepatectomy for giant haemangiomas over 10 cm in diameter. BMC
Surg. 2020;20:93.
Newhook TE, LaPar DJ, Lindberg JM, Bauer TW, Adams RB, Zaydfudim VM.
Morbidity and mortality of hepatectomy for benign liver tumors. Am J
Surg. 2016;211:102–108.
Schnelldorfer T, Ware AL, Smoot R, Schleck CD, Harmsen WS, Nagorney
DM. Management of giant hemangioma of the liver: resection versus
observation. J Am Coll Surg. 2010;211:724–730.
Terkivatan T, Vrijland WW, Den Hoed PT, etal. Size of lesion is not a criterion
for resection during management of giant liver haemangioma. Br J Surg.
2002;89:1240–1244.
Management of Benign
Liver Tumors
Richard D. Schulick, MD, MBA, and Ana Gleisner, MD, PhD
enign liver neoplasms occur in up to 20% of the population
and include cystic lesions (simple cysts and mucinous cystic
B
neoplasms [MCNs]) and solid lesions (hemangiomas, adenomas,
and focal nodular hyperplasia [FNH]). Most lesions are incidentally
discovered during imaging for other indications. When symptomatic, these lesions are associated with abdominal pain and, more
rarely, symptoms related to compression of the upper gastrointestinal tract. Symptoms are often vague, and a causal relationship
with the liver lesion can be difficult to establish. Surgical resection
of benign lesions is typically indicated if symptoms interfere with
daily living and after other conditions commonly associated with
abdominal pain, such as biliary colic and peptic ulcer disease, have
been excluded. Surgical resection is also indicated based on the risk
of rupture and hemorrhage (adenomas) and/or the risk of malignant
transformation (adenomas and MCNs). Surgeons should be familiar
with the clinical workup, imaging features, and indications for intervention for these benign liver neoplasms.
RADIOGRAPHIC EVALUATION OF
LIVER LESIONS
The use of abdominal imaging has increased more than twenty-fold
in the past four decades, resulting in the increased identification of
incidental liver lesions. The vast majority of these lesions are benign,
particularly when found in younger patients. With advances in
axial imaging technology, most benign lesions may be definitively
diagnosed with imaging alone; tissue diagnosis is rarely required.
However, because benign liver lesions differ in their potential for
malignant transformation and risk of bleeding, making the correct
diagnosis is critical to inform the need for surgical intervention.
Ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are the most commonly used modalities to
image liver lesions. Although US has the advantages of ease of use,
short duration, and absence of ionizing radiation, it has limited specificity to diagnose liver lesions, especially in the presence of steatosis
or fibrosis. For these reasons, imaging with CT or MRI is typically
required to diagnose benign liver lesions. For accurate diagnosis of
liver lesions, intravenous contrast is necessary, with three distinct
phases of enhancement: the early hepatic arterial phase, portal venous
phase, and delayed hepatic venous phase. In general, MRI has a higher
sensitivity and specificity compared with CT for liver lesions and is
often used if CT findings are equivocal. Table 1 summarizes common
radiographic findings of benign liver lesions using these three modalities. Among solid lesions, hemangiomas, adenomas, and FNH are
hypervascular, showing contrast enhancement in the arterial phase.
BENIGN LIVER CYSTS
Pathogenesis
Simple liver cysts are predominately congenital in nature, arising
from aberrant bile ducts that lack communication with the biliary
tree for drainage. Accumulation of serous, nonbilious fluid creates
a spherical, nonseptated cyst lined by a single layer of cuboidal or
columnar biliary epithelium with a surrounding fibrous stroma.
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